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|Trade names||Noristerat, others|
|Synonyms||NETE; NET-EN; Norethindrone enanthate; SH-393; 17α-Ethynyl-19-nortestosterone 17β-enanthate; 17α-Ethynylestra-4-en-17β-ol-3-one 17β-enanthate|
|AHFS/Drugs.com||International Drug Names|
|Drug class||Progestin, progestogen, progestogen ester|
|Chemical and physical data|
|Molar mass||410.598 g/mol g·mol−1|
|3D model (JSmol)|
Norethisterone enanthate (NETE), also known as norethindrone enanthate, is a form of progestogen-only injectable birth control which is used to prevent pregnancy in women. It may be used following childbirth, miscarriage, or abortion. The failure rate per year in preventing pregnancy is 2 per 100 women. Each dose lasts two months with only up to two doses typically recommended.
Side effects include breast pain, headaches, depression, irregular menstrual periods, and pain at the site of injection. Use in those with liver disease is not recommended as is use during pregnancy due to risk of birth defects. Use appears to be okay during breastfeeding. It does not protect against sexually transmitted infections. NETE is an ester and prodrug of norethisterone, through which it works. It works as a method of birth control by stopping ovulation.
Norethisterone was patented in 1951 and came into medical use in 1957. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$1.04–7.99 per 200 mg vial. It has been approved by itself in more than 60 countries including the United Kingdom and some in Europe, Central America, and Africa, and in combination with estradiol valerate in at least 36 countries mainly in Latin America. It is not available in the United States.
Side effects of NETE may include breast pain, headaches, depression, irregular menstrual periods, and pain at the site of injection. It can cause birth defects in the fetus if used during pregnancy.
NETE is a prodrug of norethisterone in the body. Upon reaching circulation, it is rapidly converted into norethisterone by esterases. Hence, as a prodrug of norethisterone, NETE has essentially the same effects as norethisterone, acting as a potent progestogen with additional weak androgenic and estrogenic activity (the latter via its metabolite ethinylestradiol). NETA has some progestogenic activity of its own, but it is unclear if NETE does similarly.
|Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PR, metribolone for the AR, estradiol for the ER, dexamethasone for the GR, aldosterone for the MR, dihydrotestosterone for SHBG, and cortisol for CBG. Footnotes: a = Metabolite of norethisterone. b = Prodrug of norethisterone and/or other active metabolites. Sources: |
|Algestone acetophenide||Synthetic||Pregnane||ND||ND||ND||NA||75–150 mg||ND|
|Hydroxyprogesterone caproate||Synthetic||Pregnane||250–500 mga||25 mg||250–500 mg||NA||250–500 mg||250 mg ≈ 10 days|
|Medroxyprogesterone acetate||Synthetic||Pregnane||50–100 mg||ND||ND||150 mg||25 mg||50 mg ≈ 14 days|
|Megestrol acetate||Synthetic||Pregnane||ND||ND||ND||NA||25 mg||ND|
|Norethisterone enanthate||Synthetic||Estrane||ND||ND||ND||200 mg||50 mg||ND|
|Progesterone (oil soln.)||Bioidentical||Pregnane||200 mgb||ND||ND||NA||NA||25 mg ≈ 2–3 days|
|Progesterone (cryst. susp.)||Bioidentical||Pregnane||50–100 mg||ND||ND||NA||NA||50 mg ≈ 14 days|
|Note: All data are for intramuscular or subcutaneous injection. Abbreviations: TFD = Endometrial transformation dose. MDT = Menstrual delay test dose (Greenblatt). OID = Ovulation-inhibiting dose (antigonadotropic effect; without an estrogen). POIC-D = Progestogen-only injectable contraceptive dose(s). CIC-D = Combined injectable contraceptive dose(s). Footnotes: a = Given in two 125- or 250-mg divided doses. b Given in ten 20-mg divided doses. Sources: |
Similarly to oral norethisterone and norethisterone acetate, intramuscular NETE has been found to form ethinylestradiol as an active metabolite. With a single intramuscular injection of 200 mg NETE in premenopausal women, the mean maximum concentration of ethinylestradiol was 32% of that of a combined oral contraceptive containing 30 μg ethinylestradiol, the maximum equivalent oral dose of ethinylestradiol observed in the first few days of exposure was 20.3 μg/day, and the mean equivalent oral dose of ethinylestradiol over 8 weeks was 4.41 μg/day. As such, the exposure to ethinylestradiol was described as markedly lower than that of an oral contraceptive containing 30 μg ethinylestradiol. The estimated conversion rate of NETE into ethinylestradiol was 0.1%, which was much lower than that observed for oral norethisterone and norethisterone enanthate (0.2–1.0%), likely due to the lack of the first-pass through the liver with parenteral administration. In accordance with the low levels of ethinylestradiol produced, no increase rates of thromboembolism or hepatic adenoma have been observed in post-authorization data of intramuscular NETE, and the medication does not resemble combined oral contraceptives containing ethinylestradiol in its safety profile.
NETE, also known as norethinyltestosterone enanthate, as well as 17α-ethynyl-19-nortestosterone 17β-enanthate or 17α-ethynylestr-4-en-17β-ol-3-one 17β-enanthate, is a progestin, or synthetic progestogen, of the 19-nortestosterone group, and a synthetic estrane steroid. It is the C17β enanthate ester of norethisterone. NETE is a derivative of testosterone with an ethynyl group at the C17α position, the methyl group at the C19 position removed, and an enanthate ester attached at the C17β position. In addition to testosterone, it is a combined derivative of nandrolone (19-nortestosterone) and ethisterone (17α-ethynyltestosterone). Esters related to NETE include norethisterone acetate and levonorgestrel butanoate.
Norethisterone enantate is the generic name of the drug and its INNM and BANM. It is also spelled as norethisterone enanthate and is also known as norethindrone enanthate (the USAN of norethisterone being norethindrone). NETE is known by its former developmental code name SH-393 as well.
NETE has been marketed alone as a progestogen-only injectable contraceptive under the brand names Depocon, Doryxas, NET-EN, Noristat, Noristerat, Norigest, and Nur-Isterate, and in combination with estradiol valerate as a combined injectable contraceptive under the brand names Chinese Injectable No. 3, Efectimes, Ginediol, Mesigyna, Mesilar, Meslart, Mesocept, Mesygest, Nofertyl, Nofertyl Lafrancol, Noregyna, Norestrin, Norifam, Norigynon, Nostidyn, Sexseg, and Solouna.
|NET only||Low (e.g., 0.35 mg)||Camila, Errin, Heather, Jencycla, Jolivette, Locilan, Micro-Novum, Micronovum, Micronor, Nor-QD, Nora, Noriday, Ortho Micronor||Progestogen-only oral contraceptive|
|NET or NETA only||High (e.g., 5 mg, 10 mg)||Aygestin, Lupaneta Pack (combination pack with leuprorelin), Norcolut, Norlutate, Primolut N, Primolut Nor, SH-420, Utovlan||Gynecological disorders and other uses|
|NETE only||Injection (e.g., 200 mg)||Depocon, Doryxas, NET-EN, Noristerat, Norigest, Nur-Isterate||Progestogen-only injectable contraceptive|
|NET or NETA with ethinylestradiol||Low (e.g., 0.4 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg)||Aranelle, Balziva, Binovum, Brevicon, Brevinor, Briellyn, Cyclafem, Dasetta, Estrostep, Femcon, Generess, Gildagia, Gildess, Jinteli, Junel, Larin, Leena, Lo Loestrin, Lo Minastrin, Loestrin, Lolo, Lomedia, Microgestin, Minastrin, Modicon, Nelova, Norimin, Norinyl, Nortrel, Ortho, Ortho-Novum, Ovcon, Ovysmen, Philith, Primella, Select, Synphase, Synphasic, Tilia, Tri-Legest, Tri-Norinyl, Trinovum, Vyfemla, Wera, Wymzya, Zenchent, Zeosa||Combined oral contraceptive|
|NET with mestranol||Low (e.g., 1 mg, 2 mg)||Norethin, Noriday, Norinyl, Norquen, Ortho-Novum, Sophia||Combined oral contraceptive|
|NETA with estradiol||Low (e.g., 0.1 mg, 0.5 mg)||Activella, Activelle, Alyacen, Cliane, Climagest, Climesse, Cliovelle, CombiPatch, Elleste Duet, Estalis, Estropause, Eviana, Evorel, Kliane, Kliofem, Kliogest, Kliovance, Mesigyna, Mesygest, Mimvey, Necon, Novofem, Nuvelle, Sequidot, Systen, Trisequens||Combined menopausal hormone therapy|
|NETE with estradiol valerate||Injection (e.g., 50 mg)||Chinese Injectable No. 3, Efectimes, Ginediol, Mesigyna, Mesilar, Meslart, Mesocept, Mesygest, Nofertyl, Nofertyl Lafrancol, Noregyna, Norestrin, Norifam, Norigynon, Nostidyn, Sexseg, Solouna||Combined injectable contraceptive|
|Abbreviations: NET = Norethisterone. NETA = Norethisterone acetate. NETE = Norethisterone enanthate. Sources: |
NETE has been approved for use alone as a progestogen-only injectable contraceptive in more than 60 countries throughout the world including in Europe, Latin America, Asia, and Africa. Specific countries in which NETE as a standalone medication is or has been available include Bangladesh, France, Germany, India, Italy, Malaysia, Mexico, the Philippines, Singapore, South Africa, Thailand, and the United Kingdom.
NETE has been approved for use in combination with estradiol valerate as a combined injectable contraceptive in at least 36 countries, mostly in Latin America but also in Africa. It is or has been available in combination with estradiol valerate in Argentina, the Bahamas, Barbados, Bolivia, Brazil, Chile, Colombia, Costa Rica, the Dominican Republic, Ecuador, Egypt, El Salvador, Ghana, Grenada, Guatemala, Guyana, Haiti, Honduras, Jamaica, Kenya, Mexico, Nicaragua, Panama, Paraguay, Peru, St. Lucia, Turkey, Uruguay, Venezuela, and Zimbabwe.
Norethisterone and its acetate and enanthate esters are progestogens that have weak estrogenic and androgenic properties.
17α-Hydroxyprogesterone caproate is a depot progestogen which is entirely free of side actions. The dose required to induce secretory changes in primed endometrium is about 250 mg. per menstrual cycle.